A Novel International Monkeypox Outbreak
Authors: Amesh Adalja, Tom Inglesby
Journal: Annals of Internal Medicine (2022)

Ideas and OpinionsAugust 2022A Novel International Monkeypox OutbreakFREEAmesh Adalja, MD and Tom Inglesby, MDAmesh Adalja, MDJohns Hopkins Center for Health Security, Baltimore, Maryland (A.A.) and Tom Inglesby, MDJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (T.I.).Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-1581 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Few clinicians practicing in the United States have ever seen a case of monkeypox infection. However, a new, unusual, multinational outbreak of monkeypox that is unfolding rapidly makes it important to know what a case might look like. This is critical not only to permitting rapid and proper medical and public health interventions but also to helping to understand the extent and spread of the outbreak. The current outbreak—which includes confirmed or suspected cases in the United States, the United Kingdom, Spain, Portugal, Italy, Belgium, Sweden, France, Canada, Australia, Germany, and the Netherlands—appears to have a pattern of spread that does not mirror past outbreaks outside of Africa, almost all of which have been related to importation via flights from Africa or exposure to infected exotic pets (1). This unusual monkeypox outbreak should prompt all clinicians to be attuned to the possibility of this infectious disease. Clinicians who suspect they may have a patient with monkeypox should contact their state or local health department immediately.The History and Characteristics of the Pathogen and IllnessMonkeypox is a member of the orthopoxvirus family, the most notable member of which is smallpox. The double-stranded DNA virus was first noted in monkeys in the 1950s and has a wide host range, notably including rodents. Human cases first came to attention during the smallpox eradication campaign (2). There are 2 distinct clades of the virus: the more virulent Congo Basin clade, and the milder West African clade. The latter has been identified in some of the cases in the current outbreak (1), including the sole case identified to date in the United States.In recent years, monkeypox outbreaks have been identified in 11 African countries, with the most cases reported in the Democratic Republic of the Congo (3). The increase in monkeypox outbreaks in recent years may be related to diminished population immunity to smallpox over time. Smallpox is closely related to monkeypox, and vaccination programs for smallpox ended decades ago (2). The highest rates of illness in Africa have historically been noted in children who had not received smallpox vaccination (2). It is also possible that changes in land use are putting more people in proximity to animals that carry the virus. The virus had not been detected outside of Africa before 2003.Monkeypox spreads through respiratory droplets, direct contact, or fomites. The Centers for Disease Control and Prevention (CDC) also notes the theoretical risk for airborne transmission and advises airborne infection control protocols to protect against this whenever possible. Such protocols include use of N95 masks and other personal protective equipment when delivering care or when otherwise in close contact with an infected person. The incubation period can range from 5 to 21 days, and a person is not contagious until symptoms begin. Historically, the chief means of transmission has been from animal contact, although human-to-human transmission does occur and has in the past led to small, contained human outbreaks (4).Severe complications can occur, including involvement of the central nervous system and airway compromise from lymphadenitis. Mortality has been reported to range from 1% to 10% but may differ in settings where advanced medical care is available (2).Notable OutbreaksOver the past 2 decades, there have been multiple international importations of monkeypox by travelers who were exposed in countries where the disease is endemic. Despite these travel-related importations, there has been little secondary human-to-human spread. In 2021, at least 2 travel-related cases occurred in the United States, with no secondary spread documented (5).Before the current outbreak, the most notable outbreak in the United States occurred in 2003 and was linked to the importation of African rats. In this outbreak, the imported animals were housed with other animals, such as prairie dogs. Approximately 4 dozen cases occurred in the United States, with no deaths and only 3 persons developing serious illness. All cases were most likely related to exposure to infected animals. Smallpox vaccine was deployed as preexposure and postexposure prophylaxis to some contacts of monkeypox cases in the course of that outbreak (6).DiagnosisGiven the current unfolding outbreak, clinicians seeing patients with new onset of febrile illness and rash should consider monkeypox, especially if lymphadenopathy is also present. The rash typically starts in the mouth, then moves to the face, followed by the extremities (including the palms and soles) in a centrifugal pattern. A definitive diagnosis is accomplished via polymerase chain reaction testing of skin lesions or fluid. These tests are available at state public health laboratories. There is no commercially available test (4).TreatmentAlthough there is no standard-of-care treatment for monkeypox, smallpox antivirals with poxvirus activity, such as cidofovir, brincidofovir, and tecovirimat, have activity against monkeypox. The latter 2 drugs have U.S. Food and Drug Administration (FDA) approval for use in smallpox treatment. Such medications would most likely be reserved for treatment of severe cases or in immunocompromised persons and would be accessed through a public health department or the CDC (4).PreventionThe smallpox vaccines are effective in the prevention of monkeypox and as postexposure prophylaxis. A newer-generation smallpox vaccine, JYNNEOS (Bavarian Nordic), has an FDA indication for the prevention of monkeypox, and the older-generation ACAM2000 can be used off-label for the same purpose. In prior outbreaks, vaccination of close contacts has successfully limited transmission. Administration of prophylactic vaccine as early as immediately after possible exposure can abort infection or significantly attenuate it. In cases in which smallpox vaccine is contraindicated, vaccinia immune globulin may be given as an alternative postexposure prophylaxis agent (4).Uncertainties Related to the Current OutbreakAs of this writing, several dozen monkeypox cases have been reported in Europe, the United Kingdom, and North America. What distinguishes these cases—all of which are outside the endemic region of the virus—is that person-to-person transmission is occurring, with the majority of cases seemingly unlinked to travel from an endemic country and the appearance of multiple, as-yet unlinked clusters. This suggests that undetected chains of transmission have been occurring.Another unusual characteristic is that a significant proportion—though not all—of the cases that have been recognized are in men who have sex with men (MSM), and many of these cases are being diagnosed at sexually transmitted infection (STI) clinics (1). This suggests that the virus may be exploiting specific social networks. The virus may or may not be spreading sexually in this group and may instead be relying on skin-to-skin contact and/or droplet respiratory transmission. Of note, the latter has been identified as a transmission pathway for meningococcus in MSM clusters.The most pressing immediate challenge is to unravel the epidemiology of this outbreak. What is driving this outbreak, which is much larger and more widespread than prior monkeypox outbreaks outside of Africa? Initial genetic analysis has not reported any genetic changes that are believed to be likely to increase transmissibility (7). Is the virus spreading through a social network? Was transmission facilitated by clustering at specific events? Rapid case investigations and case–control studies are essential to understanding this and are under way.In the meantime, containment efforts will rely on enhanced case finding, isolation, contact tracing, and postexposure vaccination. Primary care physicians, urgent care physicians, emergency medicine physicians, dermatologists, and those working in STI clinics may be the most likely to identify new patients with monkeypox should they continue to appear.References1. World Health Organization. Monkeypox - United Kingdom of Great Britain and Northern Ireland. 18 May 2022. Accessed at www.who.int/emergencies/disease-outbreak-news/item/2022-DON383 on 19 May 2022. Google Scholar2. Petersen BP, Damon IK. Orthopoxviruses. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9th Edition. Elsevier; 2020:1809-17. Google Scholar3. World Health Organization. Monkeypox. 19 May 2022. Accessed at www.who.int/news-room/fact-sheets/detail/monkeypox on 19 May 2022. Google Scholar4. Centers for Disease Control and Prevention. Clinical Recognition. Accessed at www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html on 19 May 2022. Google Scholar5. Centers for Disease Control and Prevention. Monkeypox in the United States. Accessed at www.cdc.gov/poxvirus/monkeypox/outbreak/us-outbreaks.html on 19 May 2022. Google Scholar6. Centers for Disease Control and Prevention (CDC). Update: multistate outbreak of monkeypox—Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR Morb Mortal Wkly Rep. 2003;52:642-6. [PMID: 12855947] MedlineGoogle Scholar7. Isidro J, Borges V, Pinto M, et al. First draft genome sequence of monkeypox virus associated with the suspected multi-country outbreak, May 2022 (confirmed case in Portugal). Virological. 19 May 2022. Accessed at https://virological.org/t/first-draft-genome-sequence-of-monkeypox-virus-associated-with-the-suspected-multi-country-outbreak-may-2022-confirmed-case-in-portugal/799 on 23 May 2022. Google Scholar Comments0 CommentsSign In to Submit A Comment Thomas HanscheidFaculdade de Medicina da Universiade de Lisboa24 May 2022 Outbreak in a population co-infected with HIV - possible implications? As mentioned in the article, several cases have been seen in STD clinics in MSM. As happend here two days ago, a case was seen in such a patient, who has a longstanding HIV infection. I suspcet some (many?) of the other cases might share this characteristic. As far as I can tell from the literature, previous outbreaks (and cases) were not in such a immunocompromised population, which raises the question if this co-infection does not bring a new dimension to this current outbreak? Rujittika Mungmunpuntipantip (1), Viroj Wiwanitkit (2)(1)Private Academic Consultant, Bangkok, Thailand, (2) Adjunct professor, Joseph Ayobaalola University, Ikeji-Arakeji, Nigeria; Honorary professor, Dr DY Patil University, Pune, India; visiting professor, Faculty of Medicine, University of Nis, Serbia26 May 2022 Correspondence on International Monkeypox Outbreak We would like to share ideas on the current international monkeypox outbreak problem. First, it should discuss the possibility of a global epidemic. The fundamental question is whether a pandemic like COVID-19 will occur. Many details concerning the current outbreak remain unknown at this time [2]. There is still a fallacy regarding what caused the disease to spread so quickly outside of Africa. Essentially, the disease is zoonotic, and human-to-human transmission has been reported [3]. The current scenario is complicated by the fact that the sickness may also be a new sexually transmitted infectious disease problem. Indeed, the disease manifests itself as an acute febrile sickness with skin manifestations. There is still a chance of unusual presentation, afebrile disease, and no overt symptoms. To address the issue, many governments have begun to take safeguards and check international visitors. This could be the same loop as during the early stages of the COVID-19 pandemic. If the latest monkeypox outbreak follows the pattern of a respirator-borne disease, the situation could become dire. The lesson from COVID-19 should teach us to seek knowledge as soon as possible. Early active prevention of illness transmission is required. References Adalja A, Inglesby T. A Novel International Monkeypox Outbreak. Ann Intern Med. 2022 May 24. doi: 10.7326/M22-1581. Online ahead of print. Sookaromdee P, Wiwanitkit V. BMJ rapid response. https://www.bmj.com/content/377/bmj.o1274/rr Available at Monkeypox: we still don't know about the outbreaks Wiwanitkit S, Wiwanitkit V. Atypical zoonotic pox: Acute merging illness that can be easily forgotten. J Acute Dis2018;: 7:88-89. Author, Article, and Disclosure InformationAffiliations: Johns Hopkins Center for Health Security, Baltimore, Maryland (A.A.)Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (T.I.).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1581.Corresponding Author: Amesh Adalja, MD, Johns Hopkins Center for Health Security, 621 East Pratt Street, Baltimore, MD 21202; e-mail, [email protected]edu.Author Contributions: Conception and design: A. Adalja, T. Inglesby.Analysis and interpretation of the data: A. Adalja, T. Inglesby.Drafting of the article: A. Adalja, T. Inglesby.Critical revision for important intellectual content: A. Adalja, T. Inglesby.Final approval of the article: A. Adalja, T. Inglesby.Administrative, technical, or logistic support: A. Adalja, T. Inglesby.Collection and assembly of data: A. Adalja, T. Inglesby.This article was published at Annals.org on 24 May 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAnnals On Call - Monkeypox: Should We Worry About Another Pandemic? Robert M. Centor and Amesh Adalja Metrics Cited byMonkeypox: World health emergency in 2022Rapid Adaptation of Established High-Throughput Molecular Testing Infrastructure for Monkeypox Virus DetectionThe Monkeypox Outbreak and Implications for Dental PracticeThe 2022 monkeypox outbreak: Lessons from the 640 cases in 36 countriesShould not airborne transmission be ignored in the 2022 monkeypox outbreak?Monkeypox virus under COVID-19: Caution for sexual transmission – CorrespondenceImplications of the SARS-CoV-2 subvariants BA.4 and BA.5Clinical characteristics and comparison of longitudinal qPCR results from different specimen types in a cohort of ambulatory and hospitalized patients infected with monkeypox virus.Paediatric monkeypox patient with unknown source of infection, the Netherlands, June 2022Geographic Structuring and Divergence Time Frame of Monkeypox Virus in the Endemic RegionMonkeypox: A Contemporary Review for Healthcare ProfessionalsDisease-causing human viruses: novelty and legacyMultinational monkeypox outbreak: what do we know and what should we do?Monkeypox – An emerging pandemicWhy should RNA viruses have all the fun – Monkeypox, a close relative of smallpox and a DNA virus August 2022Volume 175, Issue 8Page: 1175-1176KeywordsProphylaxisSmallpoxVaccines ePublished: 24 May 2022 Issue Published: August 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. 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